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Frontiers of Environmental Science & Engineering

ISSN 2095-2201

ISSN 2095-221X(Online)

CN 10-1013/X

Postal Subscription Code 80-973

2018 Impact Factor: 3.883

Front Envir Sci Eng    2014, Vol. 8 Issue (1) : 99-105    https://doi.org/10.1007/s11783-013-0490-7
RESEARCH ARTICLE
MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus
Lingyan HOU1, Yun LU2(), Ying LI2, Li LI1
1. College of Science, Beijing Forestry University, Beijing 100083, China; 2. State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China
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Abstract

The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA (miRNA) is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17β-estradiol (E2) induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335-5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.

Keywords estrogen      microRNA (miRNA)      microarray      biomarker     
Corresponding Author(s): LU Yun,Email:luyun@tsinghua.edu.cn   
Issue Date: 01 February 2014
 Cite this article:   
Lingyan HOU,Li LI,Yun LU, et al. MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus[J]. Front Envir Sci Eng, 2014, 8(1): 99-105.
 URL:  
https://academic.hep.com.cn/fese/EN/10.1007/s11783-013-0490-7
https://academic.hep.com.cn/fese/EN/Y2014/V8/I1/99
Fig.1  E2-stimulated uterine weight change. The uterus was weighted at 1.5h, 3h, 6h, 9h, and 12h after E2 treatment.
type of chipnumber of miRNA changed at different time points
1.5 h3 h6 h9 h12 h
Aldehyde slide7958124
Amino slide6125113
Tab.1  The number of miRNAs that have were statistically significant change from two different types of chip
Fig.2  Fold change of E2-regulated miRNAs verified by RT-PCR.
MiRNAname of target gene
Mir-451Cdkn2d
Mir-155Fgf7, Tspan14, Acta1, Ywhae, Csnk1g2, Rela, Tomm20,Smarca4, Antxr2, Upp2, Hivep2
Mir-335-5pEtf1, Rab11b, Prpf4b
Mir-365Oaz2, Nfib, Phf15, Kcnh2, Tll2, Ehf, Ppp5c, Csk, Ankrd17, Adm, Ywhae
Tab.2  Overlapped targets of E2-regulated miRNAs from the three prediction software tools
categorytop functionsfocus molecules
networkcell cycle, cell death, cellular movement18
diseases and disorderscancer9
molecular and cellular functionscell cycle8
canonical pathwayPI3K/AKT signaling3
tox listsaryl hydrocarbon receptor signaling3
Tab.3  Function analysis of the 25 predicted target genes of E2 regulated miRNAs
Fig.3  Top network function of the predicted target genes. The genes with gray background are screened out from prediction as indicated in Table 3. The different shapes represnet different functional catalogs of genes. Genes with white circle were the genes selected by Ingenuity Systems Pathway Analysis to build up the network.
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